{[5-(3,4-dimethoxyphenyl)furan-2-yl]methyl}[2-(1H-indol-3-yl)ethyl]amine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: {[5-(3,4-dimethoxyphenyl)furan-2-yl]methyl}[2-(1H-indol-3-yl)ethyl]amine
• 英文别名: N-[[5-(3,4-dimethoxyphenyl)furan-2-yl]methyl]-2-(1H-indol-3-yl)ethanamine
• 化学式: C₂₃H₂₄N₂O₃
• 分子量: 376.455
• InChiKey: PHYAZRSXCWMTCL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  28
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  59.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  5-(3,4-二甲氧基苯基)呋喃-2-甲醛 、 色胺 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以42%的产率得到{[5-(3,4-dimethoxyphenyl)furan-2-yl]methyl}[2-(1H-indol-3-yl)ethyl]amine
  参考文献：
  名称：

  Virtual screening-driven discovery of dual 5-HT6/5-HT2A receptor ligands with pro-cognitive properties

  摘要：

  A virtual screening campaign aimed at finding structurally new compounds active at 5-HT6R provided a set of candidates. Among those, one structure, 4-(5-{[(2-{5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl}ethyl) amino]methyl}furan-2-yl)phenol (1, 5-HT6R K-i = 91 nM), was selected as a hit for further optimization. As expected, the chemical scaffold of selected compound was significantly different from all the serotonin receptor ligands published to date. Synthetic efforts, supported by molecular modelling, provided 43 compounds representing different substitution patterns. The derivative 42, 4-(5-{[(2-{5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl}ethyl)amino]methyl}furan-2-yl)phenol (5-HT6R K-j= 25, 5-HT2AR K-i = 32 nM), was selected as a lead and showed a good brain/plasma concentration profile, and it reversed phencyclidine-induced memory impairment. Considering the unique activity profile, the obtained series might be a good starting point for the development of a novel antipsychotic or antidepressant with procognitive properties. (C) 2019 The Authors. Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2019.111857

文献信息

• Virtual screening-driven discovery of dual 5-HT6/5-HT2A receptor ligands with pro-cognitive properties
  作者：Jakub Staroń、Rafał Kurczab、Dawid Warszycki、Grzegorz Satała、Martyna Krawczyk、Ryszard Bugno、Tomasz Lenda、Piotr Popik、Adam S. Hogendorf、Agata Hogendorf、Krzysztof Dubiel、Mikołaj Matłoka、Rafał Moszczyński-Pętkowski、Jerzy Pieczykolan、Maciej Wieczorek、Paweł Zajdel、Andrzej J. Bojarski

  DOI：10.1016/j.ejmech.2019.111857

  日期：2020.1

  A virtual screening campaign aimed at finding structurally new compounds active at 5-HT6R provided a set of candidates. Among those, one structure, 4-(5-[(2-5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl}ethyl) amino]methyl}furan-2-yl)phenol (1, 5-HT6R K-i = 91 nM), was selected as a hit for further optimization. As expected, the chemical scaffold of selected compound was significantly different from all the serotonin receptor ligands published to date. Synthetic efforts, supported by molecular modelling, provided 43 compounds representing different substitution patterns. The derivative 42, 4-(5-[(2-5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl}ethyl)amino]methyl}furan-2-yl)phenol (5-HT6R K-j= 25, 5-HT2AR K-i = 32 nM), was selected as a lead and showed a good brain/plasma concentration profile, and it reversed phencyclidine-induced memory impairment. Considering the unique activity profile, the obtained series might be a good starting point for the development of a novel antipsychotic or antidepressant with procognitive properties. (C) 2019 The Authors. Published by Elsevier Masson SAS.